Computed tomography (CT), ultrasound, and magnetic resonance imaging have been used to image and diagnose diseases of the human heart. By gating the acquisition of the images to the heart cycle (gated imaging), these modalities enable one to produce 3D images of the heart without significant motion artifact and to more accurately calculate various parameters such as ejection fractions [1-3]. Unfortunately, these imaging modalities give inadequate resolution when investigating embryonic development in animal models. Defects in developmental mechanisms during embryogenesis have long been thought to result in congenital cardiac anomalies. Our understanding of normal mechanisms of heart development and how abnormalities can lead to defects has been hampered by our inability to detect anatomic and physiologic changes in these small (<2mm) organs. Optical coherence tomography (OCT) has made it possible to visualize internal structures of the living embryonic heart with high-resolution in two- and threedimensions. OCT offers higher resolution than ultrasound (30 um axial, 90 um lateral) and magnetic resonance microscopy (25 um axial, 31 um lateral) [4, 5], with greater depth penetration over confocal microscopy (200 um). Optical coherence tomography (OCT) uses back reflected light from a sample to create an image with axial resolutions ranging from 2-15 um, while penetrating 1-2 mm in depth [6]. In the past, OCT groups estimated ejection fractions using 2D images in a Xenopus laevis [7], created 3D renderings of chick embryo hearts [8], and used a gated reconstruction technique to produce 2D Doppler OCT image of an in vivo Xenopus laevis heart [9]. In this paper we present a gated imaging system that allowed us to produce a 16-frame 3D movie of a beating chick embryo heart. The heart was excised from a day two (stage 13) chicken embryo and electrically paced at 1 Hz. We acquired 2D images (B-scans) in 62.5 ms, which provides enough temporal resolution to distinguish end-contraction from end-relaxation. After acquiring the image set, we were able to measure the ejection fraction.

Optical coherence tomography (OCT) is an emerging medical imaging technology which can generate high resolution, cross-sectional images of tissue in situ and in real time, without the removal of tissue specimen. Although endoscopic OCT has been used successfully to identify certain pathologies in the gastrointestinal tract, the resolution of current endoscopic OCT systems has been limited to 10-15 um for clinical procedures. In this study, in vivo imaging of the gastrointestinal tract is demonstrated at a three-fold higher axial resolution (<5 um), using a portable, broadband, Cr⁴⁺:Forsterite laser as the optical light source. Images acquired from the esophagus and colon on animal model display tissue microstructures and architectural details at ultrahigh resolution, and the features observed in the OCT images are well-matched with histology. The clinical feasibility study is conducted through delivering OCT imaging catheter using the standard endoscope. OCT images of normal esophagus and Barrett's esophagus are demonstrated with distinct features.

Imaging of human autopsy samples was performed from the luminal side with a high (3.5 μm axial and 7 μm lateral) resolution OCT system (around 800 nm) or a regular (15-20 μm axial and 20 μm lateral resolution) OCT system (around 1300 nm). For each sample, dimensions were measured by histomorphometry and OCT and the optical attenuation was measured. Quantitative analysis showed a strong and significant correlation between OCT and histology cap thickness measurements for both OCT systems. For both systems, the measured attenuation coefficients of diffuse intimal thickening and lipid-rich regions differed significantly from media and calcifications. Both the high and regular resolution OCT systems can precisely image the atherosclerotic plaques. Quantitative analysis of the OCT signals allowed in situ determination of the intrinsic optical attenuation coefficient of atherosclerotic tissue components within regions of interest, which can further help to discriminate the plaque and arterial wall components.

In the past decade, optical coherence tomography (OCT) has achieved a rapid development in clinical applications. Its capability of on-line measurement, non-destructive manner and high spatial resolution offers a great potential for tissue engineering in which the dynamic process of tissue growth need to be monitored on-line either for bulk constructs or at the cellular level. In this study, two OCT systems, time-domain Michelson interferometer based OCT (TD-OCT) and whole field OCT (WF-OCT) have been used to image poly(lactic acid) based scaffold and tissue engineered bone. It is demonstrated that TD-OCT is able to visualize the porous structure of the scaffold and its changes during culture at a macroscopic level, whilst the cells' distribution and morphology can be depicted clearly in WF-OCT. With the aid of an external contrast agent, magnetic beads, clearer cellular images have been obtained.

We developed an ultra high resolution Fourier-Domain-OCT (FD-OCT) system for the use in dermatology. An axial resolution of less than 3 μm within the tissue was achieved by superimposing two broadband SLDs. FDOCT systems offer new possibilities for the design of the interferometer and the application system. Since no phase modulator is needed, the reference plane can be realized within the application system. This leads to a substantial improvement in the sensitivity against polarisation mode dispersion (PMD). It furthermore makes an elaborate chromatic dispersion matching obsolete. Two different applicaton system were compared. In the first system the reference wave was created by a plane plate just a few 100 μm above the probe. In the second approach an extra beam splitter and a mirror to generate the reference wave was used.

We present results of studies in embryology and ophthalmology performed using our ultrahigh-resolution full-field OCT system. We also discuss recent developments to our ultrashort acquisition time full-field optical coherence tomography system designed to allow in vivo biological imaging. Preliminary results of high-speed imaging in biological samples are presented. The core of the experimental setup is the Linnik interferometer, illuminated by a white light source. En face tomographic images are obtained in real-time without scanning by computing the difference of two phase-opposed interferometric images recorded by high-resolution CCD cameras. An isotropic spatial resolution of ~1 μm is achieved thanks to the short source coherence length and the use of high numerical aperture microscope objectives. A detection sensitivity of ~90 dB is obtained by means of image averaging and pixel binning. In ophthalmology, reconstructed xz images from rat ocular tissue are presented, where cellular-level structures in the retina are revealed, demonstrating the unprecedented resolution of our instrument. Three-dimensional reconstructions of the mouse embryo allowing the study of the establishment of the anterior-posterior axis are shown. Finally we present the first results of embryonic imaging using the new rapid acquisition full-field OCT system, which offers an acquisition time of 10 μs per frame.

Whole filed optical coherence microscopy system is used to image the cellular structures of highly scattering, as opposed to relatively transparent, biological tissues. The system used has imaging resolutions of 0.7 x 0.9 microns for axial x transversal directions, respectively, which represents arguably the highest resolution in the OCT filed reported so far, but with the compromise that imaging depth is less than that of the conventional OCT systems. Porcine tissues of articular cartilage and bronchus are used in the experimental demonstrations. Results demonstrate that whole filed OCT is capable of delineating faithfully the cells, nuclei and fiber bundles with an imaging depth up to 0.4 mm. It is envisaged that this technique would have an enormous applications in histopathology and other biological applications.

Full-field Fourier-domain optical coherence tomography (3F-OCT) is a full-field version of spectraldomain/swept-source optical coherence tomography. A set of two-dimensional Fourier holograms is recorded at discrete wavenumbers spanning the swept-source tuning range. The resultant three-dimensional data cube contains comprehensive information on the three-dimensional morphological layout of the sample that can be reconstructed in software via three-dimensional discrete Fourier-transform. This method of recording of the OCT signal confers signal-to-noise ratio improvement in comparison with "flying-spot" time-domain OCT. The spatial resolution of the 3F-OCT reconstructed image, however, is degraded due to the presence of a phase cross-term, whose origin and effects are addressed in this paper. We present theoretical and experimental study of imaging performance of 3F-OCT, with particular emphasis on elimination of the deleterious effects of the phase cross-term.

We have demonstrated video-rate horizontal cross-sectional (en-face) OCT imaging using a parallel heterodyne detection technique. This technique is based on a dual-channel frequency synchronous detection technique that operates a pair of CCD cameras as two-dimensional heterodyne sensor arrays. Using this technique a series of full-field en-face OCT images are acquired at a rate of 100 frames/s during a single longitudinal scan. Results of en-face OCT imaging are reported.

The authors report preliminary clinical results using a unique instrument which acquires and displays simultaneously an Optical Coherence Tomography (OCT) and an indocyanine green fluorescence image (ICGF). The two images are produced by two channels, an OCT and a confocal channel tuned to the ICG fluorescence spectrum. The system is based on our previously described ophthalmic OCT/confocal imaging system, where the same source is used to produce the OCT image and excite fluorescence in the ICG dye. The system is compact and assembled on a chin rest and it enables the clinician to visualise the same area of the eye fundus in terms of both en-face OCT slices and ICG angiograms, displayed side by side. The images are collected by fast T-scanning (en-face) which are then used to build B-scan or C-scan images. We present images of a variety of choroidal neovascular membranes, and lesions suspected of harboring choroidal neovascular membranes.

A retinal tracker was integrated into a third-generation commercial clinical optical coherence tomography system (Stratus OCT) manufactured by Carl Zeiss Meditec Inc. (CZMI). The instrument, called tracking optical coherence tomography (TOCT), uses a secondary sensing beam in a confocal reflectometer and steering mirrors to compensate eye motion with a closed loop bandwidth of 1 kHz and a lateral accuracy of less than 15 μm. Imaging and tracking control systems have been integrated into a single platform and user interface in order to admit new imaging capabilities and considerable simplification in acquisition of clinical data. The system was configured to acquire three-dimensional retinal OCT maps through all subject eye movements and blinks.

An ultrahigh resolution spectral domain optical coherence tomography (OCT) system capable of performing high speed imaging in the ophthalmology clinic has been developed. An OCT system using spectral/Fourier domain enables high speed imaging rates of up to 25,000 axial scans (A-scan) per second. Using a low threshold femtosecond Ti:sapphire laser light source, which can generate bandwidths of ~125 nm at 800 nm, cross-sectional imaging of the retina with ~3 μm axial resolution is possible. High speed imaging has been performed in the ophthalmology clinic on patients with various retinal pathologies using the ultrahigh resolution spectral domain OCT system. High pixel density OCT images containing 1024 pixels and 2048 transverse lines (A-scans) can be acquired in 0.08 seconds, which represents a ~100 fold improvement in imaging speed over previously reported time-domain ultrahigh resolution OCT systems. High speed imaging also enables three dimensional scanning and mapping of intraretinal architectural morphology with unprecedented resolution. High speed ultrahigh resolution OCT is a powerful tool for visualizing retinal pathologies, especially those involving the details of the photoreceptor segments; it will enable three-dimensional retinal imaging and the rendering of image information from volumetric data, and it has the potential to improve the early diagnosis of retinal diseases.

We present a low-cost, high resolution, real-time Spectral Domain Optical Coherence Tomography (SDOCT) system optimized for rapid 3D imaging of the human retina in vivo. Using a source with an 841nm center wavelength and a FWHM bandwidth of 49nm, 6.67 second length bursts of 100 512 x 1000 pixel images were acquired with an integration time of 50 microseconds/line and a frame rate of 16 frames/sec. Three-dimensional data sets comprising up to 4.0mm x 1.2mm x 2.45mm retinal volumes were streamed to hard disk during this brief ocular fixation interval and post-processed to create 3D volumetric images of the optic nerve head and fovea.

Spectral Optical Coherence Tomography system was used to perform clinical examinations of the human eye. Images of different pathologies were obtained with the aid of a high speed standard resolution instrument. High speed allows performing scanning with high sampling density. We show that high density lateral scanning together with standard resolution is sufficient to obtain good quality cross sectional images which enable detecting such details of the eye anatomy like the external limiting membrane.

Fourier domain techniques have increasingly gained attention in the optical coherence tomography field. This is mainly due to demonstrated sensitivities of two to three orders of magnitude greater than conventional time domain techniques. FDOCT images are plagued with two sources of ambiguity and artifact. First, complex conjugate ambiguity arises from the Fourier transform of the real-valued interferometric signal. This ambiguity causes a superposition of reflectors at positive and negative pathlength differences between the sample and reference reflectors. Secondly, the source spectral shape and sample autocorrelation terms appear at DC, there by obscuring reflectors at zero pathlength difference. In this paper, we show that heterodyne detection in swept-source OCT (SSOCT) allows for the resolution of complex conjugate ambiguity and the removal of spectral and autocorrelation artifacts. We show that frequency shifting of the reference arm optical field, by use of acousto-optic modulators, upshifts the cross-interferometric signal to a user-tunable electronic frequency that corresponds to a adjustable electronic pathlength mismatch between the interferometer arms. This electronic pathlength mismatching recenters the A-scan at an offset that can be far from DC, which effectively resolves the complex conjugate ambiguity problem. Additionally, spectral and autocorrelation terms still reside near DC, which allows them to be removed by high-pass filtering. We also show that complex conjugate ambiguity resolution via frequency shifting is immune to falloff induced by finite source linewidth in SSOCT.

We demonstrate a high-speed tunable, continuous wave laser source for Fourier domain OCT. The laser source is based on a fiber coupled, semiconductor optical amplifier and a tunable ultrahigh finesse, fiber Fabry Perot filter for frequency tuning. The light source provides frequency scan rates of up to 20,000 sweeps per second over a wavelength range of >70 nm FWHM at 1330 nm, yielding an axial resolution of ~14 μm in air. The linewidth is narrow and corresponds to a coherence length of several mm, enabling OCT imaging over a large axial range.

Optical coherence tomography (OCT) system based on optical frequency-domain reflectometry (OFDR) has been developed using a superstructure-grating distributed Bragg reflector (SSG-DBR) laser, which can tune the wavelength from 1533 to 1574 nm stepwise with tuning speed of 10micro s per 0.1 nm step. Theoretical expressions of OCT imaging by the discretely swept OFDR-OCT system are described. OFDR-OCT images are demonstrated for a few biological tissues; an extracted canine, human skin, human nail, and anterior segment of enucleated porcine eye.

A novel swept source based Fourier domain optical coherence tomography (FDOCT) system using an electro-optic phase modulator was demonstrated. The imaging range was doubled by cancellation of the mirror image. The elimination of low frequency noises due to DC and autocorrelation terms increases the sensitivity by 20 dB.

We present a high-speed full range complex spectral optical coherence tomography system, which achieves an A-scan rate of 20000 depth profiles per second. By inserting a phase modulator into the reference arm and recording of every other spectrum with a 90∞phase shift (introduced by the phase modulator) we are able to distinguish between negative and positive optical path differences. A modified two-frame algorithm eliminates the problem of suppressing symmetric structure terms in the final image. To demonstrate the performance of our system we present images of the human anterior chamber in vivo.

A novel optical scheme for a full range Fourier domain optical coherence tomography (FD-OCT) is presented. This method avoids a mechanical scan for phase-shifting (mechanical M-scan) which enables a full range FD-OCT. A tilting reference wavefront is used to make variable phase offset of spectral interferometric fringes. Several spectral fringes are detected by a two dimensional CCD camera simultaneously. One axis of the CCD camera is occupied with the optical spectral axis, and the other axis is employed for phase offset variation. A few spectral fringes are extracted and used for phase-shifting algorithm. The principle of this system is confirmed with a plane mirror sample.

We present a new computational algorithm for complex frequency domain optical coherence tomography (FD-OCT) that can effectively suppress artifacts, which are caused by uncertainty in phase shift due to errors in reference phases. The algorithm treats the phase shifting values as additional unknowns and we can determine their exact values by analyzing interference fringes using numerical least square technique. A series of simulation and experiments prove that this algorithm can effectively remove strong mirror image artifacts because it is unaffected by random phase fluctuation.

High speed complex full-range Fourier domain optical coherence tomography (FD-OCT) is demonstrated. In this FD-OCT phase modulation of a reference beam (M-scan) and transversal scanning (B-scan) are performed simultaneously. Because of this simultaneous BM-scan, this FD-OCT requires only a single A-scan for each single transversal position. The Fourier transform method is applied along the direction of the B-scan to reconstruct complex spectra, and the complex spectra compose a full-range OCT image. A simple but slow version of this FD-OCT visualizes the cross-section of a plastic plate. A modified fast version of this FD-OCT investigates a sweat duct in a finger pad in vivo, and visualizes it with 100 ms acquisition time.

A method that allows removing irrelevant elements from raw SOCT images is discussed from a theoretical point of view and its efficiency is tested on a number of real objects. Described approach is based on induced macroscopic displacement of the reference mirror and does not rely on stability of phase of analyzed signals. It could be therefore a method of choice when phase stability is impossible to achieve like for vibrating or moving objects.

Fourier Domain Optical Coherence Tomography (FD OCT) recently gained large reputation as a high speed imaging modality with increased sensitivity. Since the spectrum of the backscattered light is directly available, the method is a natural candidate for performing spectroscopic tissue analysis. Spectroscopic data is extracted by applying a windowed Fourier transform. The precision of the method is analyzed by measuring the absorbance of ICG samples sandwiched between microscope glass plates. A Ti:Sapph laser serves as light source with a spectral bandwidth of 160nm. For spectral analysis of tissue two distinct spectral regions are selected by multiplying the FD OCT signal spectrum with appropriate Gaussian window functions. One obtains two tomograms that enhance slightly different structures. Finally light sources of different spectral widths are synthesized and the resulting OCT tomograms that exhibit different axial resolutions are compared with respect to image quality and structure recognition.

Spectral-Domain Polarization-Sensitive Optical Coherence Tomography (SD-PS-OCT) is a technique developed to measure the thickness and birefringence of the nerve fiber layer in vivo as a tool for the early diagnosis of glaucoma. A clinical SD-PS-OCT system was developed and scans were made around the optic nerve head (ONH) using ten concentric circles of increasing diameter. One healthy volunteer was imaged. Retinal nerve fiber layer thickness and birefringence information was extracted from the data. Polarization-sensitive OCT images were acquired at video rate (29 frames per second (fps), 1000 A-lines / frame) and at 7 fps (1000 A-lines / frame). The last setting improved the signal to noise ratio by approximately 6 dB. Birefringence measurements on the healthy volunteer gave similar results as earlier reported values that were obtained with a time-domain setup. The measurement time was reduced from more than a minute to less than a second.

We present an Optical coherence tomography (OCT) system which records full tomograms of in vivo eye structure in parallel. A full tomogram of 256(x) x 512(z) pixels covering a sample region of 6.7mm x 3,8mm is recorded in only 1ms. A standard Superluminescent diode (SLD) is used which results a depth resolution of 17 mm. Since neither depth nor transverse scanning is necessary, the system allows capturing full tomograms with high acquisition speed and reduced motion artifacts. To the best of our knowledge we present the first in vivo tomogram obtained with full parallel FD OCT system. In order to study cross talk issues for parallel illumination the transversal resolution for a thermal light source is compared to that with an SLD.

A conventional Fourier-domain optical coherence tomography(FD-OCT) is improved to a line-field FD-OCT. The line-field FD-OCT is a conventional FD-OCT in its vertical axis, and a one-dimensional(1-D) imaging system in its lateral axis. Hence, depth and lateral information, which provide a 2-D OCT image, are simultaneously detected without any mechanical scan. Using an additional 1-D mechanical scan, which is realized by a galvano mirror in our system, a 3-D volume can be measured. Because the dimensions of mechanical scan are decreased compared with conventional FD-OCT, this system is capable of faster measurement.

We explore combining Coherent anti-Stokes Raman Scattering with Optical Coherence Tomography ranging when low numerical aperture scanning is used, and demonstrate ranging of layers in a Raman-active medium.

Molecular contrast OCT (MCOCT) is an extension of OCT in which specific molecular species are imaged based on their spectroscopic characteristics. In order to improve the sensitivity and specificity of MCOCT, several techniques have recently been introduced which depend upon coherent detection of inelastically scattered light from molecules of interest in a sample. These techniques include harmonic generation, coherent anti-Stokes Raman scattering, and several different forms of pump-probe spectroscopy. We have developed a theoretical framework to facilitate the comparison of different inelastic scattering-based contrast mechanisms for molecular contrast OCT. This framework is based upon the observation that since the noise floor is defined by the reference arm power in a shot-noise limited heterodyne detection system, the relevant comparison among the techniques is isolated to the available molecular-specific signal power. We have derived the value of the molecular contrast signal power for second harmonic generation OCT (SHOCT) and three different pump-probe OCT (PPOCT) techniques. Motivated by this analysis, we have constructed a preliminary ground state recovery pump-probe OCT system, and demonstrated its performance using rhodamine 6G as the MCOCT contrast agent.

Biomechanical elastic properties are among the many variables used to characterize in vivo and in vitro tissues. Since these properties depend highly on the micro- and macro- scopic structural organization of tissue, it is useful to understand the mechanical properties and the alterations that occur when tissues are given biomechanical stimuli by applying external forces under different circumstances. Recent advances in tissue engineering have explored and utilized the significant role that externally-applied forces play during the development of engineered tissues. However, current methods for investigating the microscopic biomechanical changes in complex three-dimensional engineered tissues have been limited. Using Optical Coherence Elastography (OCE), we map the spatially-distributed mechanical displacements and strains in a representative model of a developing engineered tissue as cells begin to proliferate and attach within a three-dimensional collagen matrix. OCE is also preformed in the complex developing tissue of the Xenopus laevis (African frog) tadpole. Displacements were quantified by a cross-correlation algorithm on pre- and post- compression images, which were acquired using Optical Coherence Tomography (OCT). The differences in strain were observed over a certain period of time in various regions. OCE was able to differentiate changes in strain over time, which correspond with cell proliferation and matrix deposition as confirmed with histological observations. By anatomically mapping the regional variation of stiffness with micron resolution, it may be possible to provide new insight into the complex process by which engineered and natural tissues develop complex structures.

A high-resolution Second Harmonic Optical Coherence Tomography (SH-OCT) system is demonstrated using a spectrum broadened femtosecond Ti:sapphire laser. An axial resolution of 4.2 μm at the second harmonic wave center wavelength of 400 nm has been achieved. Because the SH-OCT system uses the second harmonic generation signals that strongly depend on the orientation, polarization and local symmetry properties of chiral molecules, this technique provides unique contrast enhancement to conventional optical coherence tomography. The system is applied to image biological tissues like the rat-tail tendon. Images of highly organized collagen fibrils in the rat-tail tendon have been demonstrated.

We report a new algorithm for spectroscopic optical coherence tomography (SOCT) that is theoretically optimal for extracting the spectral absorption profiles from turbid media when absorbing contrast agents are used. The algorithm is based on least-squares fitting of the extracted total attenuation spectra to the known absorption spectra of the contrast agents, while suppressing the contributions from spectrally dependent scattering attenuation. By this algorithm, the depth resolved contrast agent concentration can be measured even in the presence of high scattering. The accuracy and noise tolerance of the algorithm are analyzed by Monte-Carlo simulation. The algorithm was tested using single and multi-layer tissue phantoms.

We present a new light source for parallel Optical Coherence Tomography (OCT) based on multiple waveguides written in Ti:sapphire. Each channel can generate a spectrum of 174 nm bandwidth centered at 772 nm, with an optical power on sample of 30 uW. A system depth resolution of 1.9 um is obtained, which correspond to 1.5 um in tissue.

A Superluminescent Light Emitting Diode (SLED) is an ideal optical broadband source for applications like Optical Coherence Tomography (OCT) and other fiber optic based imaging techniques. High optical output power and large optical bandwidth are key features for these devices. The short coherence length related to this large bandwidth allows the realization of OCT systems with higher sensitivity. Semiconductor devices based on quantum dots (QD) are ideally suited as the active material for SLEDs since the size dispersion typical of self-assembled growth naturally produces a large inhomogeneous broadening. The large spacing between different energy levels can lead to improved thermal stability as well. In this paper we report, ridge-waveguide devices based on five stacks of self-assembled InAs/GaAs QDs. SLED devices with output powers up to 1.5 mW emitting around 1300 nm have been realized. Spectral analysis at 20°C shows a 121 nm FWHM. Temperature characteristics in the range 10-80°C are also reported.

Continuum Generation (CG) in optical waveguides has been recently attracting widespread interest in fields requiring large spectral bandwidth such as metrology and Optical Coherence Tomography (OCT). Real time and in-vivo tissue imaging with cell resolution (Δz<1μm) is rapidly becoming the ultimate frontier of several OCT medical applications. CG wavelength and bandwidth are the pertinent criteria to obtain ultra high imaging resolution. The axial resolution in tissues is inversely proportional to the bandwidth whereas the central wavelength is chosen according to the minimum absorption of water and hemoglobin. Therefore optimal candidates for OCT low coherence sources1 are continua around 1μm as this is the zero group velocity dispersion wavelength of water. In this work we demonstrate for the first time a low-noise continuum at very low powers in high index planar waveguides pumped at 1.04 μm. Bandwidths in excess of 150 nm at -3dB are generated with launching energies <1nJ/pulse in a ~2μm² single mode ridge waveguides pumped in the normal dispersion regime. Self-Phase Modulation (SPM) had proven to be the only nonlinear process responsible for the CG. The polarization of the generated continua is highly preserved. Great flexibility in engineering waveguide dispersion, mode matching and optical functionality on chip is demonstrated by the planar approach.

Polarization-Sensitive Optical Coherence Tomography (PS-OCT) has been used to measure birefringence of biological samples, namely the retinal nerve fiber layer (RNFL). The presence of blood vessels in biological samples complicates accurate measurement of tissue birefringence as a result of the Doppler shift in fringe frequency and the shadowing effect below blood vessels due to absorption and scattering of light photons by blood. We investigate phase retardation measurement with controlled capillary blood flow overlying a birefringent sample with enhanced polarization-sensitivity optical coherence tomography (EPS-OCT). The effect of blood flow on the calculation of phase retardation and tissue birefringence was studied in the polarization domain. Light propagating through an overlying moving turbid medium (blood) undergoes single or multiple forward scattering events and a Doppler shift in presence of flow. Light propagating through an overlying medium may introduce Doppler shifts of each polarization component and/or polarization shifts or retardation of light. While undergoing multiple forward scattering, each scattering event can modify the frequency or light phase delay. In successive scattering events, potential Doppler shifts and/or polarization shifts accumulate. Light propagating within the birefringent sample undergoes multiple forward scattering events leading to phase retardation between polarization components. This paper investigates phase retardation measurement underlying physiological blood flow rates (6, 12, 18, and 24μl/min) at a range of light incident angle (0-20 deg.) on the sample. With EPS-OCT, the effect of light scattering and differential Doppler shifts between the polarization modes on the measurement of phase retardation was within our speckle noise range.

Polarization sensitive optical coherence tomography (PS-OCT) extends the concept of OCT to obtain additional information on the polarizing properties of tissue. Recently, we reported on a PS-OCT system based on transversal scanning of the probing beam across the sample, and operating at a center wavelength of 1310 nm. We now modified the instrument to allow imaging of the human retina in vivo. The instrument uses an SLD light source centered at 824 nm (FWHM bandwidth: 33 nm). A stable carrier frequency is generated by acousto optic modulators. A two-channel polarization sensitive detection unit is used to obtain amplitude and phase of the interference signals in two orthogonal polarization channels. This allows to measure and image three parameters simultaneously: reflectivity, retardation, and birefringent axis orientation. The instrument can be operated in different ways: 2D imaging along x-z or y-z planes (B-scans), along the x-y plane (C-scan), and 3D imaging are possible. Compared to our previous instrument, the imaging speed was increased by an order of magnitude. This allowed to record in vivo PS-OCT images in the fovea and nerve head region of healthy volunteers.

Doppler optical coherence tomography (DOCT) is a valuable tool for depth-resolved flow measurements in tissue. However, DOCT suffers from two disadvantages: it is insensitive to flow in the direction normal to the imaging beam, and it requires knowledge of the phase of the demodulated signal. We present an alternative method of extracting flow information, using speckle of conventional amplitude optical coherence tomography images. The two techniques can be shown to be essentially equivalent, with the distinction that speckle methods are sensitive to flow in all directions but do not provide information on the direction of flow. It is well known in other imaging modalities that moving scatterers cause a time-varying speckle pattern. Due to the pixel-by-pixel acquisition scheme of conventional OCT, time-varying speckle is manifested as a change of OCT image spatial speckle frequencies. We tested the ability of speckle to provide quantitative flow information using a flow phantom (a tube filled with Intralipid flowing at a constant volumetric flow rate). Initially, m-scans were taken at over the center of the tube. Images were averaged to reduce noise and the region corresponding to the center one-quarter of the tube lumen was selected. Sequential a-scans were concatenated, the Fourier transform performed, and a ratio of high to low spatial frequencies computed. We found that, over a range of velocities, this ratio bore a linear relation to flow velocity. For two-dimensional imaging, the program was modified to use a sliding window. Parabolic flow profile was visualized inside the tube. This study shows the feasibility of extracting quantitative flow data in all directions without phase information.

We present, to the best of our knowledge, the first ultrahigh resolution, polarization sensitive OCT images of human tissue in vivo. The system is based on a Mach Zehnder interferometer and a transversal scanning of the sample. A broadband superluminescent diode with a center wavelength of 897nm and a bandwidth (FWHM) of 155nm was used. The depth resolution of the system was measured with ~ 4 micrometer in air. The actual scanning speed of 1000 transversal lines per second enables the acquisition of an image (B-scan) consisting of 1600(x) x 1000(z) pixels in 1 second. The whole signal is recorded by a polarization sensitive detection unit at the interferometer exit which enables a phase resolved measurement. From the recorded data we were able to obtain backscattered intensity, retardation and cumulative fast axis orientation of the sample. Images of these parameters obtained from a technical sample and from a human cornea in vivo are presented.

We report the design of and results obtained by using a Field Programmable Gate Array (FPGA) to digitally process Optical Doppler Tomography signals. The processor fits into the analog signal path in an existing OCT setup. We demonstrate both Doppler frequency and envelope extraction using the Hilbert transform, all in a single FPGA. An FPGA implementation has certain advantages over a general purpose Digital Signal Processor (DSP) due to the fact that the processing elements operate in parallel as opposed to the DSP, which is primarily a sequential processor. In this paper, we demonstrate that the use of a FPGA enables sampling rates exceeding DSP-based solutions. In addition, this implementation has the important feature that calculation of the phase in addition to the amplitude of the interference fringe pattern only requires few additional resources. The proposed implementation of Doppler frequency extraction in a single FPGA is feasible for real-time Doppler OCT applications requiring high signal sampling rates.

Microfluidic devices are becoming increasingly popular for many applications, enabling biological and chemical reactions to be performed with nano- and picoliter sample volumes. Accurate measurement and monitoring of fluid flow behavior in the small channels of microfluidic systems is important for evaluating the performance of existing devices, and in the modeling and design of new microfluidic networks. We present here the results of experiments using spectral-domain optical Doppler tomography (SD-ODT) to measure fluid flow in single-layer microfluidic devices. The principles behind flow imaging with SD-ODT are reviewed, a method for velocity calibration is described, and cross-sectional and en-face images of fluid velocity in microfluidic channels are presented.

A fiber based polarization-sensitive Fourier domain optical coherence tomography system was demonstrated. The complex fringe signal containing amplitude and phase information was acquired by cancellation of DC and autocorrelation terms as well as the mirror image using an electro-optic phase modulator. The Stokes vectors of the reflected and scattered light from sample were determined by processing the analytical complex fringe signals from two perpendicular polarization-detection channels. From the Stokes vectors for four different input polarization states, the birefringence image and the polarization diversity intensity image were obtained.

We present a novel fiber-based polarization sensitive spectral domain optical coherence tomography (SD-OCT) system using a fiber optic spectral polarimetry instrument (FOSPI), which provides measurement of depth-resolved polarization state of backscattered light from a specimen with single optical frequency scanning. By inserting a FOSPI in the detection path of SD-OCT, the full set of Stokes parameters of light backscattered at the specific depth of a specimen can be obtained without any other polarization controlling components in the system and the prior knowledge of the polarization state of the light incident on the sample. The operation principle of the fiber-based polarization sensitive spectral domain optical coherence tomography is demonstrated with a Mica plate as birefringent sample.

We use polarization sensitive optical coherence tomography (PS-OCT) to monitor wound healing processes in-vitro and in-vivo, which are affected by various drugs. Five rabbit subjects are used for the in-vitro studies and another five are used for in-vivo studies. The in-vitro studies are conducted to compare the PS-OCT images with histopathology. For each subject, three biopsy lesions are created on each ear: one site is not treated (control), the second site is treated with sphingosyl phosphoryl choline (SPC), which is known to promote healing, and the last is administered with tetra acetyl phytosphingo sine (TAPS), which negatively affects the healing process. Each site is examined with a PS-OCT system and conventional histopathology at 1-, 4-, 7-, 10-, and 14-days after wound generation. The phase retardation values are quantified for all cases and our results suggest that PS-OCT may be a useful tool for visualization of collagen fiber regeneration during the healing process; therefore, various drug effects can be noninvasively monitored.

Although the phenomenon of coherent backscattering (CBS) in non-biological media has generated substantial research interest, observing CBS in biological tissue has been extremely difficult. Thus, this phenomenon has awaited its applications in tissue optics over the last two decades. Here we demonstrate depth-resolved spectroscopic elastic-light scattering measurements in tissue by use of low-coherent backscattering (LCBS) spectroscopy. The depth resolution is achieved by exploiting the nature of the LCBS peak that contains information about a wide range of tissue depths. We further demonstrate that the depth-resolved LCBS spectroscopy has the potential for identifying the location of the origin of precancerous transformations in the colon at an early, previously undetectable stage.

Low coherence techniques for characterization of the transport properties of dense scattering media are considered. First of them is based on optical coherence tomography performed in the A-scan mode and used to study the effects of dense packing and particle aggregation in dense layers of scattering particles (erythrocytes in diluted blood and polystyrene spheres in water) in the course of sedimentation. The second technique is based on speckle contrast analysis in the dependence on the coherence length of probe light. The additional polarization discrimination of detected backscattered light allows us to extend the functional abilities of the developed technique. With use of this method, the transport properties and the polarization decay parameters of tissues and tissue-like phantoms can be analyzed.

Results of comparative ex vivo measurements of backscattering from rabbit cornea made by optical coherency tomography and confocal microscopy strongly suggests the existence of small angle backscattering from the cornea. Apparently, this is associated with a zero order peak of diffraction on the corneal fibril "lattice" structure, which was first suggested by D. Maurice in 1957 as a physical basis of corneal transparency. By using water suspension of polystyrene spheres as a scattering standard, absolute values of backscattering coefficients of normally hydrated cornea for wide and small angle backscattering and degree of fibrils arrangement could be estimated.

We fit different analytical models to the OCT signal obtained from scattering Intralipid solutions in order to extract the scattering coefficient. These models are based on both single scattering models and multiple scattering models of the OCT signal. Using the statistical outcome of the fitting procedure we establish the most suitable model for each of the scattering coefficients μ_s = 2.5-26 mm^-1. Our results indicate that for our specific class of OCT systems and samples/tissues, it is justified to use the single scattering model to extract the scattering coefficient from samples with scattering coefficients up to 17 mm^-1.

Angle-resolved low coherence interferometry enables depth-resolved measurements of scattered light. The scattered light measurements can be used to recover structural information from sub-surface layers, such as the size of cell nuclei. Measurements of nuclear morphology, however, can be complicated by coherent scattering between adjacent cell nuclei. Previous studies have eliminated this component by applying a window filter to Fourier transformed data based upon the justification that the coherent scattering must necessarily occur over length scales greater than the cell nucleus size. To fully study this effect, we now present results of experiments designed to test the validity of this approach. We examine light scattered by regular cell arrays, created using stamped adhesive micro-patterned substrates. By varying the array spacing, the influence of cell-to-cell correlations on light scattering distributions is determined. The impact on nuclear morphology measurements within intact tissue samples is discussed.

An optical coherence tomography (OCT) system based on a high-speed microelectromechanical system (MEMS) mirror is presented. This scanning mirror has high-speed performance because it was actuated by vertical comb drive. The size of mirror was 600 mm x 600 mm and the resonant frequencies were between 3.5 kHz to 8 kHz. In the test of scanner itself, it was operated linearly and scanned up to 30 degree angle. The MEMS mirror also provides 2-axis scanning while occupying a very small volume with extremely low power consumption. In our study, it was integrated with conventional fiber based OCT system. Via 2-axis lateral scanning, combined with an axial scan, a volume (2 mm x 2 mm x 1.4 mm) image of tissue, including a cancerous region, from a hamster cheek pouch was obtained. The axial and lateral resolution of images are 10 mm and about 20 mm respectively.

We report a design and implementation of an Optical Coherence Tomography (OCT) system based on new topology-a probe with partial reflection from a fiber tip, connected with an all-fiber autocorrelator with Faraday mirrors. The system is made of communication fiber SMF-28 and doesn’t need any electronic means (like polarization diversity receiver) to compensate for static and dynamic polarization distortions, associated with birefringence of a flexible fiberoptic probe. Because of the system topology, it no longer requires a full optical length matching arm (reference arm) and is therefore insensitive to the probe length and wave dispersion properties. The system is implementing time-domain scanning with Doppler detection, with two piezofiber delay elements, one for AC in-depth scanning, and another for DC adjustment of coherence gate scanning range. It uses a 6 mW, 55 nm bandwidth superluminescent diode with 1300 nm central wavelength, and has 15 μm in-depth (free space) and 25 μm lateral resolution, 0.7 frames per second acquisition rate. It has a catheter-based, en face, 8 Fr diameter universal probe, suitable for endoscopic imaging. Simplicity and cost effectiveness of the new topology result in the creation of a commercially available, FDA cleared system for medical OCT imaging. Theoretical and experimental optimization of the system, including optimization of probe fiber tip "reference" reflection coefficient, has been performed. Special waveform is applied to the AC piezofiber delay line, resulting in good stability of the scanning velocity and instantaneous Doppler frequency over a 70% duty cycle, which enables use of narrow bandpass signal filtering such that signal to noise performance is optimized.

Angiogenesis in advanced breast cancers is highly distorted and heterogeneous. Non-invasive imaging that can monitor angiogenesis may be invaluable for assessing tumor response to treatment. By combining ultrasound and near infrared optical imaging, a reliable new technique has emerged for predicting tumor angiogenesis within the breast.

In optical coherence tomography (OCT), it is often assumed that the signal-to-noise ratio is limited by shot noise. However, a high data acquisition rate and a low target reflectivity require operation under high optical power. Balance detection is used with the aim to bring the noise close to shot noise regime, but this is not all the time achievable in practice. If the balance detection is ideal, the limiting factor is the beat noise. This is proportional to the stray reflectance in the object arm and inverse proportional to the effective noise bandwidth. It was often noticed that the limiting theoretical value for the S/N ratio for a given stray reflectance and optical source bandwidth could not be experimentally achieved. In the present study we develop a new model where we address this issue by taking into account the limited spectral response of fiber based balanced detection receivers. We show that due to mismatches in the balanced receiver, excess photon noise has a larger contribution than normally expected, with important implications in the maximum achievable SNR. The theoretical model developed leads to a redefinition of the effective noise bandwidth to take into account the non-flat response of the directional coupler used in the balanced stage. The model is capable to explain the limitation of SNR observed in practice when stray reflectances within the interferometer are brought to infinitesimal values. The model guides optimization of parameters in order to maximize system performance, for a given optical source power and directional coupler characteristics. In this paper we present experimental results to validate the theoretical model. Such S/N analysis is paramount in the modern OCT technology, which makes use of wide bandwidth sources in the quest for high-depth resolution.

This report presents an advanced analysis of the optics of optical coherence tomography (OCT) systems. Study indicates that spectral filtering functions are contributed by the system optics, the coupling efficiency of both sample and reference arms, and the position of the sample relative to the optics. Simulations by advanced optical software, experiments on two existing OCT systems and the modified theoretical formula demonstrate that the different optics give different filtering functions. These filtering function narrow down the spectrum, shift the center of the spectrum and drop the amplitude of the intensity. Defining a composite standard deviation and a composite center wavelength of the two filtered spectra, we developed a new formula to describe the interference term of OCT, which clearly indicates the detail of the filtering function. An experiment in an extreme condition has been investigated in one of our existing OCT systems. We placed a narrow bandwidth filter into the reference arm. The filter has a center wavelength of 1313.6 nm with a full bandwidth of 6.4nm. The light source has a center wavelength of 1292nm with a bandwidth of 34nm. Experimental resolutions are 19 microns and 85 microns, with and without filter respectively. The calculations are 21.6 and 85.5 microns, respectively, using our new formula.

The application of non-linear anisotropic diffusion to reduce the speckle noise and enhance the structural boundaries in optical coherence tomography is presented. Non-linear diffusion maximally low-pass filters those parts of the image that correspond to speckle noise, while preserving information associated with structural boundaries. It is shown that this technique is efficient to enhance the quality of optical coherence tomogram, making the accurate image quantification possible.

We present a semi-analytical model of optical coherence tomography (OCT) taking into account multiple scattering. The model rests on the assumptions that the measured portion of the backscattered sample field is spatially coherent and that the sample is motionless relative to measurement time. This allows modeling an OCT signal as a sum of spatially coherent fields with random phase arguments-constant during measurement time-caused by multiple scattering. We calculate the mean OCT signal from classical results of statistical optics and a Monte Carlo simulation. Our model is shown to be in very good agreement with a whole range of experimental data gathered in a comprehensive study of cross-talk in wide-field OCT realized with spatially coherent illumination. The study consists of depth scan measurements of a mirror covered with an aqueous suspension of microspheres. We investigate the dependence of cross-talk on important optical system parameters, as well as on some relevant sample properties. We discuss the more complex OCT models based on the extended Huygens-Fresnel principle, which rest on different assumptions since they assume partially coherent interfering fields.

The combination of wavelength multiplexing and spectral interferometry allows for the encoding of multidimensional information and its transmission over a mono-dimensional channel; for example, measurements of a surface's topography acquired through a monomode fiber in a small endoscope. The local depth of the imaged object is encoded in the local spatial frequency of the signal measured at the output of the fiber-decoder system. We propose a procedure to retrieve the depth-map by determining the signal's instantaneous frequency. First, we compute its continuous, complex-valued, wavelet transform (CWT). The frequency signature at every position is contained in the resulting scalogram. We then extract the ridge of maximal response by use of a dynamic programming algorithm thus directly recovering the object's topography. We present results that validate this procedure based on both simulated and experimental data.

The phase information inherent to spectral domain optical coherence tomography (OCT) processing can be exploited to resolve sub-coherence length displacement variations. Spectral domain phase microscopy (SDPM) is a functional extension of Fourier domain OCT whose common-path topology enables extraordinary phase sensitivity. Here we demonstrate the usefulness of SDPM in three biologically relevant applications: real-time tracking of cell surface displacements of contracting cardiac myocytes, extracting cytoplasmic flow characteristics for a single-celled organism (flow rates ~10-30μm/s), and cellular mechanical responses to cytoskeletal drug treatments. The results of these experiments are corroborated by light microscopy acquired concurrently with the SDPM data.

We have demonstrated non-contact, sub-nanometer optical measurement of neural surface displacement associated with action potential propagation without applying exogenous chemicals or reflection coatings. Signals recorded from crayfish leg nerve using a phase-sensitive optical low coherence reflectometer show that transient neural surface displacement due to action potential propagation is approximately 1 nm in amplitude and 1 ms in duration. Measured optical signals are coincident with electrical action potential arrival to the optical measurement site. Recent experiments indicate signals with similar amplitude and duration are observed in response to repetitive fast stimulation (200 stimuli/s).

Holographic optical coherence imaging of diffuse targets is an en face direct imaging modality that simultaneously illuminates and detects several hundred spatial modes. The interferences among these modes contain information on long-range structure. By using Fourier spatial filtering in Fourier-domain holography, we demonstrate the first phase-contrast en face imaging of extended tissue. This ability represents a fundamental difference between holographic optical coherence imaging (OCI) and conventional optical coherence tomography (that illuminates only a single spatial mode at a time). Channel cross-talk is separated into "interesting" speckle that carries information on long-range spatial coherences in tissue, and "uninteresting" speckle that arises from multiple scattering. Spatial coherence control of the illuminating beam can separate these two contributions. Data on multicellular tumor spheroids obtained from Fourier-domain OCI operating in a phase-contrast mode, using the knife-edge technique, are presented. We achieve -95 dB of sensitivity and nearly 50 dB of dynamic range in tissue reflection.

Functional imaging of clear and tissue-simulating phantoms using phase-resolved swept-source spectroscopic OCT (PhS-SSOCT) is described. Superior sensitivity of PhS-SSOCT technique to monitor ultra-small changes in sample refractive index is demonstrated using aqueous solutions of glucose and aqueous suspensions of polystyrene microspheres and glucose. Glucose-induced changes in the phase are found to be 0.039 rad/mM and 0.037 rad/mM in the 200 μm-thick cell for clear and turbid media, respectively, that is in good agreement with our previous data obtained using differential-phase time-domain OCT. Obtained results suggest that PhS-SSOCT has a potential for noninvasive, depth-resolved, real-time quantitative monitoring of concentrations of glucose and other analytes with high accuracy.

Complex Spectral domain Optical Coherence Tomography (CSdOCT) produces images free of parasitic mirror component which results in twofold extension of the measurement range. Complete removal of this component requires exact knowledge of the introduced phase shifts, what is usually difficult to achieve. Presented method effectively removes the mirror image, even without the knowledge of the phases. The method is applicable to any variation of CSdOCT. The 'mirror image-free' tomograms of human anterior chamber in-vivo obtained with the aid of this approach are shown.

We report a new approach in optical coherence tomography (OCT) termed full-field Fourier-domain OCT (3F-OCT). A three-dimensional image of a sample is obtained by digital reconstruction of a three-dimensional data cube, acquired using a Fourier holography recording system illuminated with a swept-source. This paper presents theoretical and experimental study of the signal-to-noise ratio of the full-field approach versus serial image acquisition approach, represented by 3F-OCT and "flying-spot" OCT systems, respectively.

Fourier Domain Optical Coherene Tomography (FD OCT) is a high speed imaging modality with increased sensitivity as compared to standard time domain (TD) OCT. The higher sensitivity is especially important, if strongly scattering tissue such as blood is investigated. Recently it could be shown that retinal blood flow can be assessed in-vivo by high speed FD OCT. However the detection bandwidth of color Doppler (CD) FDOCT is strongly limited due to blurring of the detected interference fringes during exposure. This leads to a loss of sensitivity for detection of fast changes in tissue. Using a moving mirror as a reference one can effectively increase the detection bandwidth for CD FDOCT and perform perfusion sectioning. The modality is called resonant CD FDOCT imaging. The principle of the method is presented and experimentally verified.

We designed a polarization-sensitive optical coherence tomography (PS-OCT) system to study the tissue polarization properties. The system has a dual-configuration scheme with the capability of easily switching the state of probing beam in the sample arm between linear polarization (LP) and circular polarization (CP). This setup will give four sets of 2-D tomographic data for each sample measurement, thus reveal more polarization information embedded in the biological tissue than a standard two-channel CP-configured PS-OCT system. The imaging results of LPCP-OCT for dentin and enamel of tooth samples are compared and discussed.

Polarization-sensitive optical coherence tomography (PSOCT) is an optical imaging modality that is sensitive to the birefringence properties of tissues. Birefringence is related to various biological components and therefore, polarization can provide novel contrast mechanisms for imaging. In this work, we will describe the design of a high-speed polarization sensitive optical coherence tomography system. A broadband source centered at 1310nm with 35nm bandwidth was utilized as the light source. The output power of the source and the resolution of the system were around 20mW and ~20 micrometers, respectively. To achieve high-speed scan, a rapid scan optical delay line (RSOD) was utilized in the reference arm. It provided depth scanning up to 1000 A-scan/s and controlled the carrier frequency of the interference of fridge pattern. Two galvo-mounted mirrors were used for lateral scanning of the beam. The polarization state of the incident light was altered between horizontal and vertical states by using a fast polarization rotator. The combined light from the reference and the sample arms was split into two orthogonal polarization components by a polarizing beam splitter and coupled into two single-mode optical fibers that are connected to the photodiodes. The roundtrip Jones matrix of the sample arm was measured and used to calibrate the measurements of polarization properties of the sample. The elements of the Jones matrix of the sample were calculated by the using the output Jones vectors for the incident polarization states. The performance of the system was evaluated with standard samples such as a quarter-wave plate. The animal studies are currently undertaken to assess the performance of the system in-vivo.

We have developed Fourier domain low coherence interferometry (fLCI), a novel optical interferometry method for obtaining depth-resolved spectral information, specifically for the purpose of determining the size of scatterers by measuring their elastic scattering properties. The optical system achieves depth resolution by using coherence gating, enabled by the use of a white light source in a Michelson interferometer and detection of the mixed signal and reference fields with a spectrograph. The measured spectrum is Fourier transformed to obtain the axial spatial cross-correlation between the signal and reference fields providing depth-resolution. The spectral dependence of scattering by the sample is determined by windowing the spectrum to measure the scattering amplitude as a function of wavenumber (k = 2 Pi / lambda, where lambda is the wavelength). We present a new common path confgiuration fLCI optical system and demonstrate its capabilities by presenting results which determine the size of cell nuclei in a monolayer of T84 epithelial cells.

We have developed a novel angle-resolved low coherence interferometry scheme for rapid measurement of depth-resolved angular scattering distributions. These measurements enable the determination of scatterer size via elastic scattering properties. The scheme uses spectral domain measurements where the mixed signal and reference fields are dispersed by an imaging spectrograph to achieve depth-resolved measurements upon Fourier transform of the spectral data. Angle-resolved measurements are obtained by locating the spectrograph slit in a Fourier transform plane of the scattering sample. We discuss the theoretical basis for the measurements and demonstrate the capabilities of the new technique by recording the distribution of light scattered by polystyrene microspheres. The important features of the system include the ability to detect sub-surface scattering distributions and rapid data acquisition with the entire scattering distribution recorded in 40 milliseconds. The data are used to determine the microsphere size with good accuracy. Potential application of the technique to measuring cell nuclei size in living epithelial tissues is discussed.

Optical Doppler tomography (ODT) combines Doppler velocimetry and optical coherence tomography (OCT) to obtain high-resolution cross-sectional imaging of particle flow velocity in scattering media such as the human retina and skin. Here, we present the results of a theoretical analysis of ODT where multiple scattering effects are included. The purpose of this analysis is to determine how multiple scattering affects the estimation of the depth-resolved localized flow velocity. Depth-resolved velocity estimates are obtained directly from the corresponding mean or standard deviation of the observed Doppler frequency spectrum. Thus, in the present analysis, the dependence of the mean and standard deviation of the Doppler shift on the scattering properties of the flowing medium are obtained. Taking the multiple scattering effects into account, we are able to explain previous measurements of depth-resolved retinal flow profiles where the influence of multiple scattering was observed [Yazdanfar et al., Opt. Lett. 25, 1448 (2000)]. To the best of our knowledge, no analytical model exists that are able to explain these observations.

Aligning A-scans from OCT B-scan images are of relevance in a number of applications. One important case is when producing an average A-scan profile over a given sample region to suppress the speckle noise in the reflectance profile. From fitting the average A-scan curve to a mathematical model one can then extract optical parameters, from which it might be possible for instance to discriminate between healthy and pathologic tissue. Aligning B-scans may also be appropriate in order to present OCT images in a visually consistent way appropriate for comparison between corresponding images such as OCT images of the retinal layers. Alignment is most often based on tracking the position of the boundary curve that has to be aligned. Carrying out this tracking manually is tedious when dealing with many images and it is more desirable to perform it using image-tracking algorithms. Dynamic contour models or image snakes are appropriate tools for carrying out this task. We illustrate the use of dynamic programming implementations for contour tracking and subsequent alignment and compare with the result of doing the tracking by hand. In addition we illustrate the use of contour tracking for measuring the thickness of the nerve fiber layer in retinal OCT images. With the illustrated algorithms we have produced software modules for assisting medical doctors in handling the OCT data obtained using commercial equipment.

Optical coherence tomography (OCT) images transverse resolution mostly depends on the light source spectrum width. Unfortunately, most common sources providing the required power for decent OCT image have narrow spectrum, which generate a resolution loss. It is possible, assuming the OCT system is linear shift-invariant, to consider the consequence of this spectrum narrowness as a convolution. It becomes then possible to enhance this resolution through iterative deconvolution methods (IDM). However those methods have a drawback, as they usually significantly enhance speckle, which is another consequence of the source spectrum narrowness. To compensate this, we rely on preliminary speckle filtering; and especially the adaptative ones, which provide better final results. We first studied consequences of the most popular IDM on OCT images, and then the effect of preliminary adaptive speckle filtering by different methods.

We have implemented an all-fiber optical delay line, which is composed of fiber optic components such as two linearly chirped fiber Bragg gratings, fiber optic coupler and circulator. The proposed all-fiber delay line possesses features of automatic dispersion compensation and amplified optical delay. Using the fundamental characteristics of chirped fiber Bragg gratings, the basic properties are derived to appreciate the principle of all-fiber delay line. We obtained the experimental results that reveals group delay cancellation and amplified optical delay. The non-invasive cross-sectional images of biological and transparent glass samples are acquired with the proposed all-fiber delay line, which validates the potential as an optical delay line and its feasibility for optical coherence tomography.

We investigated the influence of fiber that can support more than one propagation mode in the detection arm on the dynamic range of optical low-coherence reflectometry setup (OLCR). We theoretically and experimentally showed that the dynamic range in this case can be limited up to 20dB by parasitic spikes in the OLCR signal due to coupling of modes with different group delays. In our experiments we used MM fiber 160 cm section (core/cladding diameter 50/125 μm) and PM fiber HB980 (Δn=2*10^-4, Fibercore Ltd., UK). We also experimentally showed that the single-mode fiber in the detection arm is not altered autocorrelation field function of the source.

In the last decade, Fourier-domain optical delay lines (FD-ODL) based on pulse shaping technology have emerged as a practical device for high-speed scanning and dispersion compensation in imaging interferometry such as optical coherence tomography(OCT). In this study, we investigate the effect of first- and second-order dispersion on the photocurrent signal associated with a fiber-optic OCT system implemented using a superluminescent diode centered at 950nm±35nm, an FD-ODL, and a mirror and a layered LiTaO₃ which owns suitable dispersion characteristics to model a skin specimen. We present a practically useful method associated with FD-ODL to minimize the effect of dispersion through the OCT system and the specimen combined, and quantify the results using two general metrics for axial resolution.

In this study, a duplex scanning optical delay line is implemented and characterized for optical coherence tomography. The reference and sample arms in Michelson interferometer are simultaneously scanned by use of two identical piezoelectric transducers (PZT). It is obtained that scanning range, thermal drift, repeatability, and axial scanning velocity of duplex optical scanning delay line are distinctly superior to those of single scanning optical delay line.

A unique design approach was proposed and applied to fabricate in a single chip ultra broad bandwidth and high power Superluminescent Emitting Diodes (SLEDs) at 820 nm, 1300 nm and 1550 nm windows. More than 2.5 mW, 20 mW, and 5mW of output power with a bandwidth of more than 50nm, 80 nm and 100 nm have been obtained for 820 nm, 1300 nm and 1550 nm wavelength windows, respectively. The devices were evaluated for optical coherence domain reflectometry (OCDR) and optical coherence tomography (OCT) applications, and coherence function data is quite good with a coherence measurement out to 10 mm with negligible artifacts.

Two and three SLD diodes are grouped together in order to obtain a compounded source of wide band for OCT investigations. One SLD has a two-lobe spectrum around 840 nm and a compounded spectrum is achieved by using SLDs of smaller wavelengths. This has two advantages: (1) the smaller the wavelength the lower the loss of power through the vitreous due to water absorption; (2) medium band, standard SLDs if used bring a more significant reduction to the coherence length than their counterparts, of medium band but centered at longer wavelength. We show that it is possible to obtain high resolution OCT images with an inexpensive, compact, and easy to operate source.

We demonstrate for the first time an adaptive optics (AO) spectral OCT retina camera that acquires with unprecedented 3D resolution (2.9 μm lateral; 5.5 μm axial) single shot B-scans of the living human retina. The camera centers on a Michelson interferometer that consists of a superluminescent diode for line illuminating the subject's retinal; voice coil translator for controlling the optical path length of the reference channel; and an imaging spectrometer that is cascaded with a 12-bit area CCD array. The imaging spectrometer was designed with negligible off-axis aberrations and was constructed from stock optical components. AO was integrated into the detector channel of the interferometer and dynamically compensated for most of the ocular aberration across a 6 mm pupil. Short bursts of B-scans, with 100 Ascans each, were successfully acquired at 1 msec intervals. Camera sensitivity was found sufficient to detect reflections from all major retinal layers. Individual outer segments of photoreceptors at different retinal eccentricities were observed in vivo. Periodicity of the outer segments matched cone spacing as measured from AO flood illuminated images of the same patches of retina.

In this paper, the conventional and polarization sensitive optical coherence tomography (PS-OCT) were used to image bovine articular cartilage and diagnose degenerative joint disease. The results showed that these 2D cross-sectional OCT images that can cover an area of 6×2.8mm² (limited by scope size) with a traverse resolution of 12 μm and an axial resolution of 10 μm could assess the microstructure of articular cartilage and differentiate the abnormalities in structure. The results were confirmed by their histology. Compared to conventional OCT, PS-OCT could provide depth-resolved strokes parameter images, which reflect tissue birefringence. Both conventional and PS-OCT have high efficiency and sensitivity of osteoarthritis and cartilage injury and disease diagnosis.

Atherosclerosis is unquestionably the leading cause of morbidity and mortality in developed countries. In the mean time, the worldwide importance of acute vascular syndromes is increasing. Because collagen fiber is a critical component of atherosclerotic lesions; it constitutes up to 60% of the total atherosclerotic plaque protein. The uncontrolled collagen accumulation leads to arterial stenosis, whereas excessive collagen breakdown weakens plaques thereby making them prone to rupture finally. Thus, in this study, we present the first application, to our knowledge, of using polarization-sensitive optical coherence tomography (PS-OCT) in human atherosclerosis. We demonstrate this technique for imaging of intensity, birefringence, and fast-axis orientation simultaneously in atherosclerotic plaques. This in vitro study suggests that the birefringence change in plaque is due to the prominent deposition of collagen according to the correlation of PS-OCT images with histological counterpart. Moreover, we can acquire quantitative criteria based on the change of polarization of incident beam to estimate whether the collagen synthesized is "too much" or "not enough". Thus by combining of high resolution intensity imaging and birefringence detection makes PS-OCT could be a potentially powerful tool for early assessment of atherosclerosis appearance and the prediction of plaque rupture in clinic.